A major risk in deep circumferential burns and their characteristic rigid eschar is the development of Burn Induced Compartment Syndrome (BICS)(1,2). Compartment syndrome (CS) is defined as a condition in which increased pressure in a confined anatomical space adversely affects the circulation and threatens the function and viability of the tissues therein (3). This condition requires urgent attention and resolution, sometimes as a component of the primary resuscitation of a burn victim.
The pressure develops in Compartment Syndrome as a result of extra vascular or extra cellular fluid collection within a confined space defined by non-compliant borders, which starts to develop immediately after the tissue burn injury occurred. As the intra-compartmental pressure increases, it progressively surpasses the closure pressures of lymphatic vessels, veins and venules, capillaries and arterial vessels, causing their collapse and obstructing flow(4). Capillary closure pressure of 30 mmHg, is the accepted threshold pressure for defining a clinically meaningful compartment syndrome, which requires urgent therapeutic intervention(5,6). The BICS stops the local blood supply to the tissue with the resulting ischemia and necrosis. The mounting pressure can cause additional pressure necrosis to pressure sensitive structures (such as nerves and muscles). The hands and feet crowded with neuromuscular structures close to the skin are the most vulnerable body areas but eventually even areas such as the neck, chest and abdomen will be compressed within the tight, armor-like hard eschar interfering with vital functions such as venous drainage and breathing.
The present Standard Of Care (SOC) treatment for deep circumferential burns is an emergency, early as possible surgical escharotomy that involves performing deep incisions through the non-resilient eschar from the edges of the intact skin down to healthy tissues thus relieving the mounting pressure. This surgical procedure is difficult, requires a skilled, specifically trained and experienced surgeon, and certain surgical facilities for effectuating the escharotomy that may involve acute complications such as bleeding. This surgical procedure may result in irreversible tissue damage and poor outcome. A delay in relieving the BICS (measured sometimes in a delay as short as a few hours) will result in a permanent damage to delicate structures such as nerves and muscles and extensive propagation of tissues necrosis. Better long-term results might have been achieved in many cases, if BICS could be resolved earlier and by a simple non skill-demanding procedure. Another theoretical optional treatment for deep circumferential burns is decompression of BICS by enzymatic debridement, which has been proposed in the past but no proof of feasibility of this concept has been reported(7,8).
Considerable attention has been focused in the use of proteolytic enzymes and other chemicals to effect early debridement of devitalized tissue, resulting from burns. Chemical agents, such as tannic acid, salicylic acid, and pyruvic acid, have not led to satisfactory debridement as theses chemical agents were found to cause further injury to already damaged tissue.
Extracts derived from the stem of the pineapple plant (Ananas Comosus) have been found to selectively and effectively remove devitalized tissue. Such extracts, also named bromelain, contain various proteolytic and hydrolytic enzymes. U.S. Pat. No. 4,197,291 discloses an enzyme product obtained from bromelain capable of debridement of devitalized tissue from a mammalian host which comprises a water soluble, protein that is free of caseinolytic activity and has a peak isoelectric point of about 6. A method for debridement of devitalized tissue using this enzyme product is disclosed in U.S. Pat. No. 4,226,854. U.S. Pat. No. 4,329,430 further discloses proteolytic enzyme mixtures derived from bromelain useful for dissecting and digesting devitalized tissue. The proteolytic mixture contains escharase, a water soluble, proteinaceous material, free of caseinolytic activity. Its peak isoelectric point is about 6 and is comprised of at least two subunits, each of which has a molecular weight from about 14.3 to 15 kDa. Additional components of the mixture have a molecular weight of from about 30 to 50 kDa. U.S. Pat. No. 5,830,739 describes isolation methods of escharase from bromelain, which yield an enzymatic preparation that is capable of debridement of devitalized tissue, but has neither proteolytic activity against denatured hemoglobin, gelatin, or casein nor hydrolytic activity against hyaluronic acid or dermatan sulfate.
U.S. Pat. No. 5,106,621 discloses purified cysteine proteinases derived from pineapple plant material having a molecular weight of about 25 kDa and exhibiting activity toward a coumarylamide substrate. Particularly, U.S. Pat. No. 5,106,621 relates to the cysteine proteinases ananain and comosain, which exhibit different physicochemical characteristics distinct from bromelain. A purified thiol activated protease, named o-Bromelain, is disclosed in U.S. Pat. No. 5,387,517, and is shown to have debridement activity. In addition, bromelain contains an acid phosphatase and a peroxidase and may contain amylase and cellulase activity. U.S. Pat. No. 6,335,427 teaches the purification of a 25 kDa protein from bromelain, the protein has been found to have anti-cancer activity.
EP 0296787 discloses absorbent adhesive dressings for use in treating wounds of the ulcer or burn type where there are significant wound exudates. Specifically, EP 296787 is concerned with a dressing made in the form of a three layer sandwich type construction having an occlusive film as the outer layer, an absorbent layer of fibers as the middle layer, and a wet-stick adhesive as the inner, wound-facing layer. The adhesive dressing may optionally contain a debriding enzyme on that part of the outer adhesive surface which contacts the wound.
EP 0194647 discloses a debriding tape, made from an occlusive or semi-occlusive, non-gel, non-bioerodible, surgical adhesive tape which contains on the adhesive mass surface of said surgical adhesive tape a debriding enzyme (either a proteolytic or a non-proteolytic enzyme useful for debridement of eschar and necrotic tissue) in dry, powdered form.
None of the above patents disclose an effective method or means for enzymatic escharotomy in burn induced compartment syndrome of a burned limb. There is an unmet need for application means and appropriate methods for rapid and efficient escharotomy using enzymatic escharotomy agents on the surface of burned skin area such as an affected limb or other body areas of a burn victim.